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Lack of agonistic activity in McN-A343 may be circumstantial
1Department of Physiology and Pharmacology, Tel Aviv University, Sackler School of Medicine, Israel.
Abstract:
1. In Tyrode (Ca++ 1.80 mM) or Krebs (Ca++ 3.36 mM) solution, McN-A343 evoked a dose-dependent contractile response in the naive guinea-pig ileum in the dose range 0.40-40 microM, or bladder in the dose range 0.8-200 microM. 2. After two full cycles of carbachol or bethanechol administration in Tyrode solution, neither preparation responded to McN-A343 for 45 to 60 min. The response in Krebs solution, however, was almost unaltered at 15-30 min. The rate of recovery of the contractile response appears to depend on the calcium content of the medium used. 3. A previous report that McN-A343 failed to evoke a contractile response in the guinea-pig ileum or bladder must be reconsidered in the light of the present findings.
Insights
McN-A343 causes dose-dependent contractions in guinea-pig ileum and bladder. Recovery from tachyphylaxis is faster in higher calcium solutions, suggesting calcium
Area of Science:
- Pharmacology
- Physiology
Background:
- McN-A343 is a muscarinic agonist.
- Previous studies reported McN-A343 failed to evoke contractile responses in guinea-pig ileum and bladder.
Purpose of the Study:
- To investigate the contractile effects of McN-A343 on guinea-pig ileum and bladder.
- To explore the influence of calcium concentration on McN-A343-induced responses and tachyphylaxis.
Main Methods:
- Dose-response studies of McN-A343 on isolated guinea-pig ileum and bladder preparations.
- Assessment of tachyphylaxis and recovery in Tyrode and Krebs solutions with varying calcium concentrations.
Main Results:
- McN-A343 demonstrated a dose-dependent contractile effect on both naive ileum (0.40-40 microM) and bladder (0.8-200 microM).
- Tachyphylaxis to McN-A343 was observed after repeated carbachol/bethanechol administration.
- Recovery from tachyphylaxis was significantly faster in Krebs solution (3.36 mM Ca++) compared to Tyrode solution (1.80 mM Ca++).
Conclusions:
- The contractile response to McN-A343 is dependent on calcium concentration.
- The rate of recovery from tachyphylaxis is influenced by extracellular calcium levels.
- Previous negative findings regarding McN-A343's efficacy require re-evaluation.